The differential diagnostic model for serous peptidomics in HBV carriers established by MALDI-TOF-MS analysis

Abstract

Objectives: Hepatitis B virus (HBV) can result in asymptomatic carrier (AsC) state or chronic inflammation of liver, which depends on the host immunity. We therefore investigated the peptidomic profiling in the process of HBV infection.

Design and methods: In this study, serum from 116 HBV infected (AsC and chronic hepatitis), 60 HBV-immunized and 70 normal subjects was treated with MB-WCX (weak cation exchange based magnetic beads) kits and analyzed by the Clinprot/Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) techniques. Purified serous proteins were subjected to FT-ICR-MS analysis, and Western blot further confirmed the results.

Results: The specific model comprised of two peptides m/z 2882.89 and 4476.12 could distinguish HBV infected from healthy (HBV-immunized and normal) group and showed 95.5% of the sensitivity and 95.4% of the specificity by cross-validation analysis. 40/56 HBV infected and 43/50 healthy subjects could be correctly classified by the model. The area under the receiving operating curves (AUROC) of m/z 2882.89 and 4476.12, identified as subunits of fibrinogen beta chain (FBG) Bβ10-42 and nucleophosmin (NPM) respectively, were both up to 0.88 when discriminating AsC from the healthy group. The expression of Bβ10-42 and NPM decreased significantly in the plasma of HBV infected individuals by Western blot analysis.

Conclusions: There were specific serum peptide profilings for host responses to HBV infection, and m/z 2882.89 and 4476.12 could be valuable follow-up and prognostic tools for HBV infection.

Keywords: ALB; ALP; ALT; AST; AUC; AsC; Asymptomatic carrier; FGB; Fibrinogen beta chain; HBV; Hepatitis B Virus; MALDI-TOF-MS; MB-WCX; Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry; NPM; Nucleophosmin; ROC; alanine aminotransferase; albumin; alkaline phosphatase; aspartate aminotransferase; asymptomatic HBV carriers; fibrinogen beta chain; hepatitis B virus; nucleophosmin; receiver operating characteristic; the area under the ROC curve; weak cation exchange based magnetic beads.